Nucleophilic vs Alpha addition

[deleted388502]

Really simple question:

How do you know whether something attacks the carbonyl or alpha carbon? Feel like I'm missing something big here.

Thanks.

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[Czarcasm]

Really simple question:

How do you know whether something attacks the carbonyl or alpha carbon? Feel like I'm missing something big here.

Thanks.

The alpha hydrogen of a carbonyl group is relatively acidic and therefore can be deprotonated. This results in a lone pair that resides on the alpha carbon, which can now act as a nucleophile and attack some other electrophile. Also, as you hinted, the carbonyl group carbon is partially positive and therefore a good electrophile. Any good nucleophile can attack at this position. Essentially all you're doing is looking for the electrophile and nuclephile and asking yourself, what typically happens and where.

There is a special scenario when you have a double bond between the alpha beta carbons (for example. an alpha-beta unsaturated ketone). In this instance, because of resonance, there is a partial positive charge that resides on the beta carbon and this too can be attacked by nucleophiles. As it turns out, in this type of scenario, where you have two potentially good electrophiles on a certain molecule, nucleophiles can react selectively for one region vs. the other, but this is not something that's required to know.

 

[deleted388502]

The alpha hydrogen of a carbonyl group is relatively acidic and therefore can be deprotonated. This results in a lone pair that resides on the alpha carbon, which can now act as a nucleophile and attack some other electrophile. Also, as you hinted, the carbonyl group carbon is partially positive and therefore a good electrophile. Any good nucleophile can attack at this position. Essentially all you're doing is looking for the electrophile and nuclephile and asking yourself, what typically happens and where.

There is a special scenario when you have a double bond between the alpha beta carbons (for example. an alpha-beta unsaturated ketone). In this instance, because of resonance, there is a partial positive charge that resides on the beta carbon and this too can be attacked by nucleophiles. As it turns out, in this type of scenario, where you have two potentially good electrophiles on a certain molecule, nucleophiles can react selectively for one region vs. the other, but this is not something that's required to know.

So when you do have a carbonyl with a good nucleophile, how do you know when the product will be formed by attack at the alpha carbon or carbonyl carbon?

 

[Czarcasm]

So when you do have a carbonyl with a good nucleophile, how do you know when the product will be formed by attack at the alpha carbon or carbonyl carbon?

You have to consider what you're being told. In organic chemistry, there could potentially a whole variety of different side reactions occuring. For the MCAT, it will typically be the most obvious product because they want to test your understanding.

If you're told you have some ketone, and to that ketone you added a grignard, you should immediately recognize that a ketone can act as a good electrophile, the grignard a good nucleophile (it could of been any nucleophile, I just chose this as an example). Together they'll unite in holy matrimony to produce a product (with the nucleophile attached at the carbonyl).

On the other hand, if again you're told you have some ketone, and to that ketone a base was added? What do you suppose this base will do? Well, you might recall the alpha hydrogen is relatively acidic and can be deprotonated (becoming a reasonable nucleophile). What is electrophilic that it could attack? Well, it wouldn't attack itself, but considering there's so much of its protonated form floating around (which can act as a good electrophile), that's where it'll probably go.

It's relatively straightforward if you recognize the patterns and trends. The MCAT is a multiple choice test so it further simplifies things for you and greatly reduces the need to think about all the different types of scenarios that are possible. Usually you can eliminate some incorrect answers too.